Calcium-activated potassium channels sustain calcium signaling in T lymphocytes - Selective blockers and manipulated channel expression levels

To maintain Ca2+ entry during T lymphocyte activation, a balancing efflux of cations is necessary. Using three approaches, we demonstrate that this cation efflux is mediated by Ca2+-activated K+ (K-Ca) channels, hSKCa2 in the human leukemic T cell line Jurkat and hIKCa1 in mitogen-activated human T cells. First, several recently developed, selective and potent pharmacological inhibitors of K-Ca channels but not K-V channels reduce Ca2+ entry in Jurkat and in mitogen-activated human T cells. Second, dominant negative suppression of the native K-Ca channel in Jurkat T cells by overexpression of a truncated fragment of the cloned hSKCa2 channel decreases Ca2+ influx. Finally, introduction of the hIKCa1 channel into Jurkat T cells maintains rapid Ca2+ entry despite pharmacological inhibition of the native small conductance K-Ca channel. Thus, K-Ca channels play a vital role in T cell Ca2+ signaling.